CN1239451C - Process for preparing chiral desubstituted carbinol with high selectivity - Google Patents
Process for preparing chiral desubstituted carbinol with high selectivity Download PDFInfo
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- CN1239451C CN1239451C CN 02111215 CN02111215A CN1239451C CN 1239451 C CN1239451 C CN 1239451C CN 02111215 CN02111215 CN 02111215 CN 02111215 A CN02111215 A CN 02111215A CN 1239451 C CN1239451 C CN 1239451C
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Abstract
The present invention relates to a new method for preparing chiral disubstituted carbinol with high yield and high stereoselectivity, which uses metallic boron hydride as a reducing agent and reduces prochiral ketone under the action of louis acid and chiral ligands according to catalytic amount to prepare the chiral disubstituted carbinol. The method uses the metallic boron hydride with the advantages of low cost, easy obtainment and easy preservation as the reducing reagent, so that expensive boron and hydrogen with high toxicity are not needed. The chiral ligands used in the method are all natural, cheap and easy to obtain. Thereby, the method with low cost and environment protection is provided for preparing the chiral disubstituted carbinol.
Description
Technical field
The present invention relates to the method that a kind of novel reduction system high yield and highly-solid selectively ground prepare chiral, secondary alcohols, this reduction system is a kind of composite metal complex, by metal hydroborates M (BH
4)
n/ Louis acid Lewisacids/ chiral ligand, this reduction system can prepare chiral, secondary alcohols by the catalysis prochiral ketone.
Technical background
Having optically active chiral, secondary alcohols is the important organic compound of a class, and they are usually as chiral intermediate, and chiral auxiliary reagent or part use.As the strong means of a kind of preparation chiral, secondary alcohols, the asymmetric reduction of prochiral ketone is subjected to organic chemist's attention always.Now, people have been developed multiple method of reducing.Wherein, be one of successful method by the catalytic asymmetric hydroboration of chirality azoles quinoline of Itsuno and Corey development.But,, therefore, seek cheap and nontoxic method of reducing and paid close attention to by people always because this class reaction must face the toxicity of borine and the costliness of price.
M (BH
4)
nBe a class cheap and stable go back original reagent.In organic reaction, usually be used for the reduction of carbonyl compound and undersaturated carboritride.Be used for the asymmetric reduction prochiral ketone for it, up to now, the report of a routine catalytic reduction only arranged.Nineteen ninety-five, people such as Japanization scholar T.Mukaiyama reported use KBH
4Reduction prepares the method (T.Nagata, K.Yorozu, T.Yamada and T.Mukaiyama, Angew.Chem.Int.Ed.Engl.1995,34,2145) of chiral, secondary alcohols under chirality salen-Co (II) katalysis.
Summary of the invention
The purpose of this invention is to provide a kind of novel reduction system [metal hydroborates M (BH
4)
n/ Louis acid NX
m/ chiral ligand] prepare the method for chiral, secondary alcohols.This reduction system can prepare chiral, secondary alcohols by the catalysis prochiral ketone.
In organic solvent with a certain proportion of metal hydroborates M (BH
4)
nWith Louis acid NX
mMixing can obtain a kind of novel original reagent of going back, it under the chiral ligand effect of catalytic amount, can high yield and highly selective reduce various prochiral ketones and obtain chiral, secondary alcohols.
The mol ratio of prochiral ketone and reduction system is 1 among the present invention: 1-8.
Metal hydroborates M (BH among the present invention
4)
n/ Louis acid NX
mMolar ratio be controlled at 1: best between the 8-0.2.
Chiral ligand metal hydroborates M (BH among the present invention
4)
nRatio control 1: between the 0.5-200, wherein 1: the reaction effect between the 5-100 is best.
Among the present invention with an organic solvent with tetrahydrofuran (THF), methylene dichloride and toluene for well.
When being controlled between room temperature-reflux temperature, temperature of reaction of the present invention can obtain best reaction result.
Described prochiral ketone molecular formula is RCOR
1, the chiral, secondary alcohols molecular formula is RCOHR
1R=C wherein
1-12Alkyl, substituted-phenyl PhR
2, phSO
2Or PhSO
2CH
2Described alkyl is alkyl, cyclohexyl, the phenyl or naphthyl of straight chain, side chain.R
1=C
1-12Alkyl, C
PH
2P+1NO
2, C
pH
2p+1NR
3R
4R wherein
2=NO
2, CN, X, OCH
3Or CF
3P＝1-3。R
3Or R
4=H or C
PH
2P+1
Described chiral ligand metal hydroborates M (BH
4)
nIn, M=monovalence or divalent metal are as lithium, sodium, potassium, Gai, Magnesium, zinc etc., n=1-2.
Described Louis acid NX
mIn, N=Sn, Zr, Ti and Al, X=halogen, m=1-4.
Chiral ligand of the present invention has following molecular formula:
Asymmetric reduction with methyl phenyl ketone is discussed temperature respectively as model reaction, solvent, catalyzer and M (BH
4)
nSame NX
mRatio to the reaction influence.
At first, be used as catalyzer and investigate temperature, solvent, catalyzer and M (BH
4)
nSame NX
mRatio to the reaction influence.Operation is as follows: add M (BH in the reaction solvent of investigating
4)
nWith a certain proportion of NX
m, stir under the room temperature after 1 hour, add 2 (10mol%) of catalytic amount, reflux 0.5 hour slowly drips the solution of this reaction solvent of methyl phenyl ketone again under the equality of temperature.Reaction finishes, and conventional processing promptly gets product.Reaction result is shown in table-1.From then on reaction result is learnt:
(1) in certain reaction solution, the stereoselectivity of reaction raises along with the temperature of reacting and increases.
(2) under same reaction soln and identical temperature of reaction, the stereoselectivity of reaction depends on M (BH
4)
nSame NX
mRatio.
(3) different reaction solvent is to the difference that influences of reaction.Under the backflow situation, be reflected at when carrying out among the THF, the gained stereoselectivity is best, secondly is toluene, and the poorest is CH
2Cl
2
(4) NX
mReaction there is certain influence.As SnCl
2, SnCl
4, ZrCl
4, TiCl
4And AlCl
3Deng obtaining better effects.
Table-1: temperature, solvent and M (BH
4)
nThe influence of molar ratio with Louis acid to reacting
| M(BH 4) n | NX m | Molar ratio [M (RH 4) n/NX m] | Solvent | Temperature (℃) | Productive rate (%) | Ee (％) |
| KBH 4 KBH 4 KBH 4 KBH 4 KBH 4 KBH 4 KBH 4 KBH 4 KBH 4 KBH 4 KBH 4 KBH 4 NaBH 4 NaBH 4 NaBH 4 NaBH 4 NaBH 4 LiBH 4 Zn(BH 4) 2 LiBH 4 Ca(BH 4) 2 NaBH 4 NaBH 4 NaBH 4 NaBH 4 KBH 4 KBH 4 Zn(BH 4) 2 LiBH 4 | SnCl 2 SnCl 2 SnCl 2 SnCl 2 SnCl 2 SnCl 2 SnCl 2 SnCl 2 SnCl 2 SnCl 2 SnCl 2 SnCl 4 SnCl 2 SnCl 2 AlCl 3 SnCl 4 TiCl 4 SnCl 2 SnCl 2 SnCl 2 SnCl 2 LiCl ZnCl 2 ZrCl 4 CuCl 2 TiCl 4 AlCl 3 SnCl 4 SnCl 4 | 8 4 2 1.5 1 0.5 0.2 2 2 2 2 4 2 2 3 4 4 2 1 2 1 3 2 4 2 4 3 2 4 | Oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane toluene carrene oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane oxolane | Backflow backflow backflow backflow backflow backflow backflow room temperature 40-50 backflow backflow backflow room temperature refluxes | 80 89 93 92 94 90 93 93 95 92 94 96 98 98 96 98 97 98 97 96 98 93 93 96 0 96 93 97 96 | 36 57 96 95 89 80 78 56 91 35 5 92 53 96 58 95 73 97 96 96 95 0 5 60 0 68 61 93 95 |
Investigating temperature, solvent and M (BH
4)
n/ NX
mAfter the influence of molar ratio to reaction, we have studied the influence (Fig. 1) of different chiral ligands to reaction.Here the asymmetric reduction of still having selected methyl phenyl ketone for use reacts the M (BH that adopts as model reaction
4)
nThe equivalence ratio of/methyl phenyl ketone is 1.1: 1.The reaction result example is in table-2.Catalyst levels in the table-2 is relative methyl phenyl ketone.
Table-2: different chiral ligands is to the influence of reaction
| M(BH 4) n/NX m/ molar ratio | Chiral ligand | Consumption (mol%) | Productive rate (%) | Ee(％) |
| KBH 4/SnCl 2/2 KBH 4/SnCl 2/2 KBH 4/SnCl 2/2 KBH 4/SnCl 2/2 KBH 4/SnCl 4/4 KBH 4/SnCl 2/3 LiBH 4/SnCl 2/ KBH 4/SnCl 2/2 | 1 2 2 2 2 2 2 2 | 10 10 20 40 100 200 5 2 | 94 96 95 94 93 95 96 98 | 64 96 95 98 97 96 94 92 |
| KBH 4/SnCl 2/2 | 2 | 1 | 96 | 91 |
| KBH 4/SnCl 2/2 | 2 | 10 | 95 | 96 |
| LiBH 4/SnCl 4/4 | 2 | 10 | 93 | 93 |
| NaBH 4/TiCl 4/4 | 2 | 20 | 94 | 69 |
| NaBH 4/AlCl 3/3 | 2 | 15 | 96 | 67 |
| Zn(BH 4) 2/SnCl 2/1 | 2 | 20 | 94 | 92 |
| KBH 4/SnCl 2/2 | 2 | 0.5 | 97 | 87 |
| KBH 4/SnCl 2/2 | 3 | 10 | 96 | 61 |
| KBH 4/SnCl 2/2 | 4 | 10 | 92 | 81 |
| KBH 4/SnCl 2/2 | 5 | 10 | 95 | 86 |
| KBH 4/SnCl 2/2 | 5 | 1 | 94 | 71 |
| NaBH 4/SnCl 2/2 | 5 | 10 | 94 | 89 |
| KBH 4/SnCl 2/2 | 6 | 10 | 96 | 0 |
| KBH 4/SnCl 2/2 | 7 | 10 | 95 | 5 |
| NaBH 4/SnCl 2/2 | 8 | 10 | 95 | 95 |
| NaBH 4/ZrCl 4/4 | 8 | 10 | 94 | 94 |
| KBH 4/SnCl 2/2 | 8 | 10 | 97 | 96 |
| KBH 4/SnCl 2/2 | 9 | 10 | 94 | 53 |
From reaction result, chirality β-amine alcohols part can provide stereoselectivity preferably, the stereoselectivity that wherein provides best (95%ee).And, in this reaction, can not obtain good result for chiral diol class part (as part 6 and 7).
The reduction system that the present invention uses is the metal hydroborates M (BH that is easy to get by industrial
4)
n(n=1-2), Louis acid NX
mForm from natural chiral ligand with main.Raw materials used stable and cheap.Operation is simple, is easy to industrial production.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
The preparation of embodiment 1. chirality 1-phenylethyl alcohols
(a) with tindichloride (0.6mmol), POTASSIUM BOROHYDRIDE (1.2mmol), tetrahydrofuran (THF) (8mL) adds in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 98%.[α]
D 20＝+52.4(c2.04，CHCl
3)，96％ee；IR：3354(OH)，3086，3029，1452，1078；
1HNMR(CDCl
3，TMS)：δ1.39(3H，d，CH
3)，2.92(1H，s，OH)，4.74(1H，q，CHOH)，7.20-7.35(5H，m，Ph)；m/z 122(M
+)，107，79，78，77，51.
(b) with tindichloride (0.6mmol), POTASSIUM BOROHYDRIDE (1.2mmol), tetrahydrofuran (THF) (8mL) adds in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 8 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 97%.[α]
D 20＝-52.6(c 2.73，CHCl
3)，96％ee。
(c) with tindichloride (0.6mmol), sodium borohydride (1.2mmol), tetrahydrofuran (THF) (8mL) add in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 98%.[α]
D 20＝+52.9(c1.64，CHCl
3)，96％ee。
(d) with tin tetrachloride (0.3mmol), POTASSIUM BOROHYDRIDE (1.2mmol), tetrahydrofuran (THF) (8mL) adds in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 96%.[α]
D 20＝+50.1(c1.65，CHCl
3)，92％ee。
(e) with aluminum chloride (0.4mmol), sodium borohydride (1.2mmol), tetrahydrofuran (THF) (8mL) add in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 96%.[α]
D 20＝-33.4(c1.07，CHCl
3)，58％ee。
(f) with titanium tetrachloride (0.3mmol), POTASSIUM BOROHYDRIDE (1.2mmol), tetrahydrofuran (THF) (8mL) adds in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 97%.[α]
D 20＝+42.5(c1.73，CHCl
3)，73％ee。
(g) with zirconium tetrachloride (0.3mmol), POTASSIUM BOROHYDRIDE (1.2mmol), tetrahydrofuran (THF) (8mL) adds in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 96%.[α]
D 20+38.2(c1.34，CHCl
3)，60％ee。
(h) with tindichloride (0.6mmol), zinc borohydride (0.5mmol), tetrahydrofuran (THF) (8mL) add in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 97%.[α]
D 20＝+53.8(c1.78，CHCl
3)，96％ee。
(i) with tindichloride (0.6mmol), hydroboration calcium (0.6mmol), tetrahydrofuran (THF) (8mL) add in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 98%.[α]
D 20＝+51.5(c1.89，CHCl
3)，95％ee。
(j) with tindichloride (0.6mmol), lithium borohydride (1.2mmol), tetrahydrofuran (THF) (8mL) add in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.1mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 96%.[α]
D 20+52.3(c1.57，CHCl
3)，97％ee。
(k) with tindichloride (0.6mmol), lithium borohydride (1.2mmol), tetrahydrofuran (THF) (8mL) add in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (0.05mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 96%.[α]
D 20＝+50.3(c1.93，CHCl
3)，94％ee。
(l) with tin tetrachloride (0.3mmol), POTASSIUM BOROHYDRIDE (1.2mmol), tetrahydrofuran (THF) (8mL) adds in the reaction flask, under the room temperature, stirred 1 hour, add catalyzer 2 (100mmol) then, reflux slowly drips tetrahydrofuran (THF) (8mL) solution of methyl phenyl ketone (1.0mmol) after half an hour.Finish, get back to room temperature, add the shrend reaction of going out, filter, filtrate is spin-dried on Rotary Evaporators, column chromatography, colourless oil liquid, productive rate is 96%.[α]
D 20＝+52.3(c1.57，CHCl
3)，97％ee。
The preparation of embodiment 2. chirality 1-phenyl propanols
Experimental procedure is with 1 (a).Colourless oil liquid, productive rate 97%.[α]
D 20=+52.4 (c 2.32, CHCl
3), 81%ee; IR:3363 (OH), 1062,898cm
-1 1H NMR (CDCl
3): δ 0.92 (3H, t, CH
3), 1.65-1.90 (2H, m, CH
2), 1.93 (1H, s, OH), 4.58 (1H, t, CHOH), 7.25-7.35 (5H, m, Ph).
Embodiment 3. chirality 1-(4-bromophenyl) ethanol preparation
Experimental procedure is with 1 (g).Colourless oil liquid, productive rate 97%.[α]
D 20=+21.6 (c1.78, MeOH), 75%ee; IR:3340 (OH), 1060,898,828cm
-1 1H NMR (CDCl
3): δ 1.38 (3H, d, CH
3), 3.20 (1H, s, OH), 4.73 (1H, q, CHOH), 7.1-7.4 (4H, m, p-BrC
6H
4).
Embodiment 4. chirality 1-(4-p-methoxy-phenyl) ethanol preparation
Experimental procedure is with 1 (a).Colourless oil liquid, productive rate 97%.[α]
D 20=+52.4 (c1.46, CHCl
3), 84%ee; IR:3380 (OH), 1063,891,834cm
-1 1H NMR (CDCl
3): δ 1.40 (3H, d, CH
3), 2.67 (1H, s, OH), 3.73 (3H, s, OCH
3), 4.78 (1H, q, CHOH), 6.8-7.2 (4H, m, p-MeOC
6H
4).
Embodiment 5. chirality 1-(4-nitrophenyl) ethanol preparation
Experimental procedure is with 1 (k).Colourless oil liquid, productive rate 97%.[α]
D 20＝+32.9(c1.24，CHCl
3)，97％ee；IR：3347(OH)，1073，902，829cm
-1；
1H NMR(CDCl
3)：δ1.33(3H，d，CH
3)，2.87(1H，s，OH)，4.75(1H，q，CHOH)，7.1-7.4(4H，m，p-NO
2C
6H
4).
Embodiment 6. chirality 1-(2-naphthyl) ethanol preparation
Experimental procedure is with 1 (b).White solid, productive rate 97%.[α]
D 20＝+32.6(c1.86，EtOH)，96％ee；IR：3338(OH)，1064，891，832cm
-1；
1H NMR(CDCl
3)：δ1.65(3H，d，CH
3)，2.18(1H，bs，OH)，5.06(1H，q，CHOH)，7.5-7.9(7H，m，C
10H
7).
Embodiment 7. chirality 2-chloro-1-phenyl-ethanol preparation
Experimental procedure is with 1 (a).Colourless oil liquid, productive rate 97%.[α]
D 20＝+35.9(c2.18，n-hexane)，92％ee；IR：3343(OH)，1063，898，828cm
-1；
1H NMR(CDCl
3)：δ3.00(1H，bs，OH)，3.52(2H，d，CH
2Cl)，4.79(1H，t，CHOH)，7.32(5H，m，Ph).
The preparation of embodiment 8. chirality 2-bromo-1-phenylethyl alcohols
Experimental procedure is with 1 (h).Colourless oil liquid, productive rate 97%.[α]
D 20＝+41.8(c1.64，CHCl
3)，94％ee；IR：3340(OH)，1057，893cm
-1；
1H NMR(CDCl
3)：δ1.43(2H，d，CH
2Br)，2.71(1H，s，OH)，4.71(1H，t，CHOH)，7.21-7.32(5H，m，Ph).
The preparation of embodiment 9. chirality 3-chloro-1-phenyl propanols
Experimental procedure is with 1 (a).White solid, productive rate 97%.[α]
D 20＝+17.4(c 1.34，CHCl
3)，81％ee；IR：3331(OH)，3228，1069，912cm
-1；
1H NMR(CDCl
3)：δ1.98-2.14(2H，m，-CH
2-)，2.73(1H，s，OH)，3.48-3.66(2H，m，CH
2Cl)，7.23-7.35(5H，m，Ph).
Embodiment 10. chirality 3-methyl-2-butanols preparation
Experimental procedure is with 1 (l).Steaming slip colourless liquid, productive rate 95%.[α]
D 20＝+0.78(c 5.03，EtOH)，78％ee；IR：3431(OH)，1040cm
-1；
1H NMR(CDCl
3)：δ0.92(6H，d，CH(CH
3)
2)，1.05(3H，d，CH
3)，1.33(1H，m，OH)，1.65(1H，m，CH)，3.53(1H，m，CHOH).
Embodiment 11. chiralitys 3,3 '-dimethyl-2-butanols alcohol preparation
Experimental procedure is with 1 (a).Steaming slip colourless liquid, productive rate 96%.[α]
D 20＝+42.7(c 3.94，CCl
4)，96％ee；IR：3400(OH)，1100cm
-1；
1H NMR(CDCl
3)：δ0.82(9H，s，C(CH
3)
3)，1.02(3H，d，CH
3)，2.78(1H，s，OH)，3.36(1H，q，CHOH).
The preparation of embodiment 12. chirality 2-butanols
Experimental procedure is with 1 (a).Get colourless liquid, productive rate 98%.[α]
D 20＝+4.5(c 4.64，MeOH)，42％ee；IR：3420(OH)，1150cm
-1；
1H NMR(CDCl
3)：δ0.93(3H，t，CH
3)，1.21(3H，d，CH
3)，1.66(2H，m，-CH
2-)，2.64(1H，s，OH)，3.56(1H，CHOH).
The preparation of embodiment 13. chirality 1-cyclohexyl ethyl alcohols
Experimental procedure is with 1 (c).Get colourless liquid, productive rate 98%.[α]
D 20＝+2.8(c 1.94，CHCl
3)，68％ee；IR：3620(OH)，3340，2860，1450cm
-1；
1H NMR(CDCl
3)：δ0.73-1.88(12H，m，c-C
6H
11 andOH)，1.21(3H，d，CH
3)，3.56(1H，CHOH).
Embodiment 14. chirality 1-phenyl-2-benzene sulphur sulfuryl-ethanol preparation
Experimental procedure is with 1 (a).White solid, productive rate 97%.[α]
D 20=+20.9 (c 2.08, CHCl
3), 95%ee; IR:3343 (OH), 1286,1135cm
-1 1H NMR (CDCl
3): δ δ 3.25 and 3.40 (each 1H, dd, CH
2), 3.69 (1H, s, CHOH), 5.19 (1H, dd, CH), 7.29-7.73 (10H, m, 2Ph).
Embodiment 15. chirality 1-(4-p-methoxy-phenyl)-2-benzene sulphur sulfuryl-ethanol preparation
Experimental procedure is with 1 (a).White solid, productive rate 98%.[α]
D 20=+10.9 (c1.38, CHCl
3), 91%ee; IR:3442 (OH), 1302,1145cm
-1 1H NMR (CDCl
3): δ 3.22 and 3.40 (each 1H, dd, CH
2), 3.60 (1H, s, CHOH), 3.70 (3H, s, CH
3), 5.12 (1H, dd, CH), 7.14-7.73 (9H, m, 2Ph).
Embodiment 16. chirality 1-(4-chloro-phenyl-)-2-benzene sulphur sulfuryl-ethanol preparation
Experimental procedure is with 1 (l).White solid, productive rate 96%.[α]
D 20=+15.3 (c1.17, CHCl
3), 96%ee; IR:3363 (OH), 1283,1155cm
-1 1H NMR (CDCl
3): δ 3.21 and 3.42 (each 1H, dd, CH
2), 3.61 (1H, s, CHOH), 3.74 (3H, s, CH
3), 5.15 (1H, dd, CH), 7.24-7.69 (9H, m, 2Ph).
Embodiment 17. chirality 1-(4-fluorophenyl)-2-benzene sulphur sulfuryl-ethanol preparation
Experimental procedure is with 1 (a).White solid, productive rate 98%.[α]
D 20=+20.9 (c 1.43, CHCl
3), 96%ee; IR:3353 (OH), 1298,1133cm
-1 1H NMR (CDCl
3): δ 3.21 and 3.36 (each 1H, dd, CH
2), 3.62 (1H, s, CHOH), 5.17 (1H, dd, CH), 7.18-7.76 (9H, m, 2Ph).
Embodiment 19. chirality 1-cyclohexyl-2-benzene sulphur sulfuryl-ethanol preparation
Experimental procedure is with 1 (a).White solid, productive rate 97%.[α]
D 20＝+23.7(c1.19，CHCl
3)，92％ee；IR：3513，2926，1285，1141cm
-1；
1H NMR(CDCl
3)：δ0.67-1.18(5H，m)，1.29-1.46(1H，m)，1.54-1.67(5H，m)，3.12(1H，s)，3.13(1H，d，)，3.32(1H，d)，3.85(1H，s)，7.31-7.74(5H，m).
Embodiment 20. chirality 1-benzene sulphur sulfuryls-3,3 '-dimethyl-2-butanols preparation
Experimental procedure is with 1 (a).White solid, productive rate 96%.[α]
D 20＝+43.6(c 3.13，CHCl
3)，99％ee；IR：3530(OH)，1286，1135cm
-1；
1H NMR(CDCl
3)：δ0.90(9H，s)，3.02(1H，dd)，3.16(1H，s)，3.19(1H，s)，3.68(1H，d)，7.32-7.55(5H，m).
Embodiment 21. chirality 1-benzene sulphur sulfuryls-2-butanols preparation
Experimental procedure is with 1 (a).White solid, productive rate 98%.[α]
D 20＝+17.9(c1.24，CHCl
3)，91％ee；IR：3503(OH)，2932，1286，1145cm
-1；
1H NMR(CDCl
3)：δ0.92(3H，t)，1.53-1.63(2H，m)，3.17-3.20(1H，m)，3.37(1H，s)，4.09(1H，m)，7.38-7.82(5H，m).
Embodiment 22. chirality 1-phenyl-2-nitro-ethanol preparation
Experimental procedure is with 1 (k).The pale yellow oily liquid body, productive rate 97%.[α]
D 20＝+25.6(c 1.16，EtOH)，89％ee；IR：3352(OH)，1288，1135cm
-1；
1H NMR(CDCl
3)：δ3.42(2H，d)，3.51(1H，s)，4.79(1H，t)，7.32-7.54(5H，m，Ph).
Embodiment 23. chirality 1-phenyl-2-(dimethylamino)-ethanol preparation
Experimental procedure is with 1 (a).White solid, productive rate 97%.[α]
D 20＝+15.9(c 2.13，EtOH)，86％ee；IR：3343(OH)，3120，2934，1291，1132cm
-1；
1H NMR(CDCl
3)：δ2.34(6H，s)，2.53-(2H，d)，4.52(1H，s)，4.79(1H，d)，7.46(5H，m，Ph).
Claims (4)
1 one kinds of highly selectives prepare the method for chiral, secondary alcohols, it is characterized in that in organic solvent a certain proportion of metal hydroborates M (BH
4)
nWith Louis acid NX
mUnder the chiral ligand effect of catalytic amount, the reduction prochiral ketone obtains chiral, secondary alcohols, and the mol ratio of prochiral ketone and reduction system is 1: 1-8, metal hydroborates M (BH
4)
nWith Louis acid NX
mMol ratio be 1: 8-0.2, chiral ligand and metal hydroborates M (BH
4)
nMol ratio be 1: 0.5-200, temperature of reaction is room temperature-reflux temperature;
Described chiral, secondary alcohols molecular formula is (H) R of RC (OH)
1, R=C wherein
1-12Alkyl, substituted-phenyl PhR
2, PhSO
2Or PhSO
2CH
2, described alkyl is alkyl, cyclohexyl, the phenyl or naphthyl of straight chain, side chain, R
1=C
1-12Alkyl, CPH
2PNO
2, C
pH
2pNR
3R
4, R wherein
2Be NO
2, CN, X, OCH
3Or CF
3, P=1-3, R
3Or R
4Be H or C
PH
2P+1
Described chiral ligand metal hydroborates M (BH
4)
nIn, M=monovalence or divalent metal, n=1-2;
Described Louis acid NX
mIn, N=Sn, Zr, Ti or Al, X=halogen, m=1-4;
Described chiral ligand has following molecular formula:
Or
2 a kind of highly selectives as claimed in claim 1 prepare the method for chiral, secondary alcohols, it is characterized in that described chiral ligand and metal hydroborates M (BH
4)
nMol ratio be 1: 5-100.
3 a kind of highly selectives as claimed in claim 1 prepare the method for chiral, secondary alcohols, it is characterized in that described organic solvent is tetrahydrofuran (THF), methylene dichloride and toluene.
4 a kind of highly selectives as claimed in claim 1 prepare the method for chiral, secondary alcohols, it is characterized in that described chiral ligand metal hydroborates M (BH
4)
nIn, M is lithium, sodium, potassium, Gai, Magnesium or zinc.
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| CN102796134B (en) * | 2012-08-31 | 2015-07-01 | 甘肃皓天化学科技有限公司 | Preparation method for Maxacalcitol intermediate |
| CN105272896A (en) * | 2015-10-19 | 2016-01-27 | 山东国润生物医药有限公司 | Preparation method of ((2S)-2-aziridinyl) benzhydrol |
| CN108947877B (en) * | 2018-08-09 | 2020-04-24 | 三峡大学 | Chiral β -hydroxy sulfone and preparation method thereof |
| CN113135814B (en) * | 2021-04-28 | 2022-08-02 | 温州大学 | Method for synthesizing chiral 1, 2-diol compound |
| WO2023097690A1 (en) * | 2021-12-03 | 2023-06-08 | 广东莱佛士制药技术有限公司 | Method for preparing b-nitro or azido alcohol by means of high-selectivity asymmetric catalytic carbonyl reduction |
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